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1.
Commun Biol ; 7(1): 1033, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174819

RESUMO

The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30-60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections.


Assuntos
Modelos Animais de Doenças , Infecções por Pseudomonas , Pseudomonas aeruginosa , Infecções Respiratórias , Animais , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Camundongos , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Feminino , Humanos , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/uso terapêutico
2.
Surg Open Sci ; 20: 94-97, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38973811

RESUMO

Liposomal bupivacaine (LB) has been used in multimodal pain management regimens to improve postsurgical analgesia. This retrospective cohort analysis assessed clinical and economic outcomes of LB vs non-LB analgesia in minimally invasive colorectal resection surgery using real-world patient data from the IQVIA linkage claims databases. Patients who received LB were 1:1 matched to patients who did not receive LB (non-LB) via propensity scores. Outcomes included opioid use during the perioperative (2 weeks before surgery to 2 weeks after discharge), continued (>2 weeks to 3 months after discharge), and persistent (>3 months to 6 months after discharge) periods and healthcare resource utilization (HRU) during the first 3 months after discharge. Mean opioid consumption was lower in the LB (n = 4397) versus non-LB (n = 4397) cohort perioperatively (483 vs 538 morphine milligram equivalents [MMEs]; P = 0.001) and after discharge within ∼3 months (222 vs 328 MMEs; P < 0.0001) and 3-6 months (245 vs 384 MMEs; P < 0.0001). The LB cohort had shorter mean length of stay (5.2 vs 5.7 days; P < 0.0001) and fewer inpatient readmissions (odds ratio [OR], 0.71; P < 0.0001), emergency department visits (OR, 0.78; P < 0.0001), and outpatient/office visits (OR, 0.91; P = 0.028) than the non-LB cohort 3 months after discharge. These data suggest use of LB in minimally invasive colorectal resection surgery may reduce perioperative and postdischarge opioid use as well as HRU. Although additional studies are needed to confirm these findings, this analysis provides valuable real-world data from large claims databases to evaluate clinical and economic outcomes that complement other types of retrospective and prospective studies.

3.
Spine J ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38843956

RESUMO

BACKGROUND CONTEXT: Perioperative pain management affects cost and outcomes in elective spine surgery. PURPOSE: This study investigated the association between liposomal bupivacaine (LB) and outpatient spine surgery outcomes, including perioperative, postoperative, and postdischarge opioid use and healthcare resource utilization. STUDY DESIGN: This was a retrospective comparative study. PATIENT SAMPLE: Eligibility criteria included adults with ≥6 months of continuous data before and after outpatient spine procedures including discectomy, laminectomy, or lumbar fusion. Patients receiving LB were matched 1:3 to patients receiving non-LB analgesia by propensity scores. OUTCOME MEASURES: Outcomes included (1) opioid use in morphine milligram equivalents (MMEs) during the perioperative and postdischarge periods and (2) postdischarge readmission and emergency department (ED) visits up to 3 months after surgery. Generalized linear mixed-effects modeling with appropriate distributions was used for analysis. METHODS: Deidentified data from the IQVIA linkage claims databases (2016-2019) were used for the analysis. This study was funded by Pacira BioSciences, Inc. RESULTS: In total, 381 patients received LB and 1143 patients received non-LB analgesia. Baseline characteristics were well balanced after propensity score matching. The LB cohort used fewer MMEs versus the non-LB cohort before discharge (80 vs 132 MMEs [mean difference, -52 MMEs; p=.0041]). Following discharge, there was a nonsignificant reduction in opioid use in the LB cohort versus the non-LB cohort within 90 days (429 vs 480 MMEs [mean difference, -50 MMEs; p=.289]) and from >90 days to 180 days (349 vs 381 MMEs [mean difference, -31 MMEs; p=.507]). The LB cohort had significantly lower rates of ED visits at 2 months after discharge versus the non-LB cohort (3.9% vs 7.6% [odds ratio, 0.50; p=.015]). Postdischarge readmission rates did not differ between cohorts. CONCLUSIONS: Use of LB for outpatient spine surgery was associated with reduced opioid use at the hospital and nonsignificant reduction in opioid use at all postoperative timepoints examined through 90 days after surgery versus non-LB analgesia. ED visit rates were significantly lower at 60 days after discharge. These findings support reduced cost and improved quality metrics in patients treated with LB versus non-LB analgesia for outpatient spine surgery.

4.
Plast Reconstr Surg Glob Open ; 12(6): e5874, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38855138

RESUMO

Background: Liposomal bupivacaine (LB) can be used for postsurgical analgesia after breast reconstruction. We examined real-world clinical and economic benefits of LB versus bupivacaine after deep inferior epigastric perforator (DIEP) flap breast reconstruction. Methods: This retrospective cohort study used the IQVIA claims databases to identify patients undergoing primary DIEP flap breast reconstruction in 2016-2019. Patients receiving LB and those receiving bupivacaine were compared to assess opioid utilization in morphine milligram equivalents (MMEs) and healthcare resource utilization during perioperative (2 weeks before surgery to 2 weeks after discharge) and 6-month postdischarge periods. A generalized linear mixed-effects model and inverse probability of treatment weighting method were performed. Results: Weighted baseline characteristics were similar between cohorts (LB, n = 669; bupivacaine, n = 348). The LB cohort received significantly fewer mean MMEs versus the bupivacaine cohort during the perioperative (395 versus 512 MMEs; rate ratio [RR], 0.771 [95% confidence interval (CI), 0.677-0.879]; P = 0.0001), 72 hours after surgery (63 versus 140 MMEs; RR, 0.449 [95% CI, 0.347-0.581]; P < 0.0001), and inpatient (154 versus 303 MMEs; RR, 0.508 [95% CI, 0.411-0.629]; P < 0.0001) periods; postdischarge filled opioid prescriptions were comparable. The LB cohort was less likely to have all-cause inpatient readmission (odds ratio, 0.670 [95% CI, 0.452-0.993]; P = 0.046) and outpatient clinic/office visits (odds ratio, 0.885 [95% CI, 0.785-0.999]; P = 0.048) 3 months after discharge than the bupivacaine cohort; other all-cause healthcare resource utilization outcomes were not different. Conclusions: LB was associated with fewer perioperative MMEs and all-cause 3-month inpatient readmissions and outpatient clinic/office visits than bupivacaine in patients undergoing DIEP flap breast reconstruction.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38733254

RESUMO

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

6.
Microsurgery ; 44(4): e31184, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747121

RESUMO

BACKGROUND: Successive osteoseptocutaneous fibula transfers for jaws reconstruction are rare but important options. This study contributes patient-reported and clinical outcomes, as well as systematically reviews all existing reports. METHODS: All sequential fibula transfers performed by the senior author were reviewed from a prospectively managed database, including University of Washington quality of life (UWQoL). Systematic review was conducted in PubMed and Cochrane databases for similar publications. RESULTS: Eighteen patients (average age 51.5 years) received sequential fibulas (mean 4.7 years between reconstructions). Secondary fibulas more often had benign indications (72.2% vs. 33.3%, p = .04), most commonly osteoradionecrosis (38.9%). At a mean follow-up of 30.5 months, the average interincisal distance increased from 21.8 to 27.6 mm, and 92.3% tolerated an oral diet following the second fibula. Eight patients completed the UW-QoL before and after the second fibula, and three prior to the first fibula. Composite physical function was significantly decreased from 96.7 prefibula reconstruction to 63.3 following the first (p < .001) and 64.2 after the second fibula (p < .001). There were no differences in other domains. The systematic review yielded six articles reporting 56 patients (mean 39 months between fibulas). Secondary fibulas were performed for repeat malignancy (45%) and osteoreadionecrosis (39%), resulting in elevated tube feeding from 20% following the first to 39% following the second, but overall high quality of life in two studies. CONCLUSIONS: Sequential osteoseptocutaneous fibula reconstructions of jaws are often performed for benign indications such as osteoradionecrosis. Overall function and QoL are comparable with those following the first fibula transfer.


Assuntos
Fíbula , Retalhos de Tecido Biológico , Qualidade de Vida , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Ósseo/métodos , Fíbula/transplante , Retalhos de Tecido Biológico/transplante , Reconstrução Mandibular/métodos
7.
Ann Plast Surg ; 92(6): 658-662, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38718341

RESUMO

PURPOSE: This study aimed to evaluate quality of life (QOL) in patients with locally advanced oral cancer who underwent surgical resection followed by simultaneous double free flap reconstruction. METHODS: Institutional database was reviewed from 2015 to 2021 and prospectively collected University of Washington Quality of Life data that were extracted for patients who met the inclusion criteria. Mean, composite, and best percentage scores were computed. Wilcoxon signed rank test was used to analyze differences between groups. RESULTS: Thirteen patients completed the assessment, all of them being male with a mean follow-up of 2.2 ± 1.2 years. Most common double free flap combination was fibula osteoseptocutaneous flap and anterolateral thigh flap (n = 11). Improvement in pain ( P = 0.01) domain score with decline in speech ( P = 0.01) and taste ( P = 0.02) was noted along with an overall decline in QOL ( P = 0.001) after cancer diagnosis. A decrease in physical function was seen postoperatively. Chewing and saliva were the most cited postoperative patient-reported domain affecting QOL. CONCLUSIONS: In double free flap reconstructed patients, in the postoperative phase, pain scores improved, whereas speech and taste scores declined. The overall health-related QOL declined compared with before cancer diagnosis.


Assuntos
Retalhos de Tecido Biológico , Neoplasias Bucais , Procedimentos de Cirurgia Plástica , Qualidade de Vida , Humanos , Masculino , Neoplasias Bucais/cirurgia , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Idoso , Adulto , Estudos Retrospectivos , Feminino , Resultado do Tratamento
9.
Ann Intern Med ; 177(5): 658-666, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38639546

RESUMO

DESCRIPTION: The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients' values and preferences, and costs. METHODS: This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications. The Clinical Guidelines Committee prioritized the following outcomes, which were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach: all-cause mortality, major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, progression of chronic kidney disease, serious adverse events, and severe hypoglycemia. Weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis and were not rated with GRADE. AUDIENCE AND PATIENT POPULATION: The audience for this clinical guideline is physicians and other clinicians. The population is nonpregnant adults with type 2 diabetes. RECOMMENDATION 1: ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence). • Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure. • Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke. RECOMMENDATION 2: ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Hipoglicemiantes , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/agonistas , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Adulto , Quimioterapia Combinada , Insulina/uso terapêutico
10.
Br J Surg ; 111(2)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38298070

RESUMO

BACKGROUND: To restore sensation after breast reconstruction, a modified surgical approach was employed by identifying the cut fourth intercostal lateral cutaneous branch, elongating it with intercostal nerve grafts, and coapting it to the innervating nerve of the flap or by using direct neurotization of the spared nipple/skin. METHODS: This was a retrospective case-control study including 56 patients who underwent breast neurotization surgery. Breast operations included immediate reconstruction after nipple-sparing mastectomy (36 patients), skin-sparing mastectomy (8 patients), and delayed reconstruction with nipple preservation (7 patients) or without nipple preservation (5 patients). Patients who underwent breast reconstruction without neurotization were included as the non-neurotization negative control group. The contralateral normal breasts were included as positive controls. RESULTS: The mean(s.d.) monofilament test values were 0.07(0.10) g for the positive control breasts and 179.13(143.31) g for the breasts operated on in the non-neurotization group. Breasts that underwent neurotization had significantly better sensation after surgery, with a mean(s.d.) value of 35.61(92.63) g (P < 0.001). The mean(s.d.) sensory return after neurotization was gradual; 138.17(143.65) g in the first 6 months, 59.55(116.46) g at 7-12 months, 14.54(62.27) g at 13-18 months, and 0.37(0.50) g at 19-24 months after surgery. Two patients had accidental rupture of the pleura, which was repaired uneventfully. One patient underwent re-exploration due to a lack of improvement 1.5 years after neurotization. CONCLUSION: Using the lateral cutaneous branch of the intercostal nerve as the innervating stump and elongating it with intercostal nerve grafts is a suitable technique to restore sensation after mastectomy. This method effectively innervates reconstructed breasts and spares the nipple/skin with minimal morbidity.


Assuntos
Neoplasias da Mama , Mamoplastia , Mastectomia Subcutânea , Transferência de Nervo , Humanos , Feminino , Mastectomia/métodos , Neoplasias da Mama/cirurgia , Mamilos/cirurgia , Estudos de Casos e Controles , Estudos Retrospectivos , Nervos Intercostais/cirurgia , Mamoplastia/métodos , Mastectomia Subcutânea/métodos
11.
Ann Plast Surg ; 92(1S Suppl 1): S27-S32, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38285992

RESUMO

BACKGROUND: Patients with traumatic brain injuries (TBIs) often experience concurrent facial bone fractures. In 2021, a prediction model with 10 variables was published and precisely predicted concomitant facial fractures in TBI patients. Herein, external validation and simplification of this model was performed. METHODS: Traumatic brain injury patients treated at a major referral trauma center were retrospectively reviewed for 1 year. The original prediction model (published in 2021), which was developed from a rural level II trauma center, was applied for external validation. A new and simplified model from our level I trauma center was developed and backwardly validated by rural level II trauma center data. RESULTS: In total, 313 TBI patients were enrolled; 101 (32.3%) had concomitant facial fractures. When the previous prediction model was applied to the validation cohort, it achieved acceptable discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.713 and good precision, with a Brier score of 0.083. A new and simplified model with 6 variables (age, tooth rupture, epistaxis, facial lesion, eye injury, and intracranial hemorrhage) was created with excellent discrimination (AUC = 0.836) and good precision (Brier score of 0.055). The backward validation of this new model also showed excellent discrimination in the cohort used to develop the original model (AUC = 0.875). CONCLUSION: The original model provides an acceptable and reproducible prediction of concomitant facial fractures among TBI patients. A simplified model with fewer variables and the same accuracy could be applied in the emergency department and at higher- and lower-level trauma centers.


Assuntos
Lesões Encefálicas Traumáticas , Fraturas Cranianas , Humanos , Estudos Retrospectivos , Fraturas Cranianas/complicações , Fraturas Cranianas/diagnóstico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Curva ROC , Centros de Traumatologia
12.
JAMA ; 329(15): 1296-1307, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37071090

RESUMO

Importance: Skin cancer is the most common cancer type and is a major cause of morbidity. Objective: To systematically review the benefits and harms of screening for skin cancer to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from June 1, 2015, through January 7, 2022; surveillance through December 16, 2022. Study Selection: English-language studies conducted in asymptomatic populations 15 years or older. Data Extraction and Synthesis: Two reviewers independently appraised the articles and extracted relevant data from fair- or good-quality studies; results were narratively summarized. Main Outcomes and Measures: Morbidity; mortality; skin cancer stage, precursor lesions, or lesion thickness at detection; harms of screening. Results: Twenty studies in 29 articles were included (N = 6 053 411). Direct evidence on screening effectiveness was from 3 nonrandomized analyses of 2 population-based skin cancer screening programs in Germany (n = 1 791 615) and suggested no melanoma mortality benefit at the population level over 4 to 10 years' follow-up. Six studies (n = 2 935 513) provided inconsistent evidence on the association between clinician skin examination and lesion thickness or stage at diagnosis. Compared with usual care, routine clinician skin examination was not associated with increased detection of skin cancer or precursor lesions (5 studies) or stage at melanoma detection (3 studies). Evidence on the association between clinician skin examination and lesion thickness at detection was inconsistent (3 studies). Nine studies (n = 1 326 051) found a consistent positive association between more advanced stage at melanoma detection and increasing risk of melanoma-associated and all-cause mortality. Two studies (n = 232) found little to no persistent cosmetic or psychosocial harms associated with screening. Conclusions and Relevance: A substantial nonrandomized evidence base suggests a clear association between earlier stage at skin cancer detection and decreased mortality risk. However, nonrandomized studies suggest little to no melanoma mortality benefit associated with skin cancer screening with visual skin examination in adolescents or adults and no association between routine clinician skin examination and earlier stage at melanoma detection. Evidence is inconsistent regarding whether clinician skin examination is associated with thinner melanoma lesions at detection.


Assuntos
Detecção Precoce de Câncer , Melanoma , Neoplasias Cutâneas , Adolescente , Adulto , Humanos , Detecção Precoce de Câncer/efeitos adversos , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/métodos , Melanoma/diagnóstico , Exame Físico/efeitos adversos , Exame Físico/métodos , Neoplasias Cutâneas/diagnóstico
13.
Sci Transl Med ; 15(693): eabp9528, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37099633

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and rapidly fatal interstitial lung disease marked by the replacement of lung alveoli with dense fibrotic matrices. Although the mechanisms initiating IPF remain unclear, rare and common alleles of genes expressed in lung epithelia, combined with aging, contribute to the risk for this condition. Consistently, single-cell RNA sequencing (scRNA-seq) studies have identified lung basal cell heterogeneity in IPF that might be pathogenic. We used single-cell cloning technologies to generate "libraries" of basal stem cells from the distal lungs of 16 patients with IPF and 10 controls. We identified a major stem cell variant that was distinguished from normal stem cells by its ability to transform normal lung fibroblasts into pathogenic myofibroblasts in vitro and to activate and recruit myofibroblasts in clonal xenografts. This profibrotic stem cell variant, which was shown to preexist in low quantities in normal and even fetal lungs, expressed a broad network of genes implicated in organ fibrosis and showed overlap in gene expression with abnormal epithelial signatures identified in previously published scRNA-seq studies of IPF. Drug screens highlighted specific vulnerabilities of this profibrotic variant to inhibitors of epidermal growth factor and mammalian target of rapamycin signaling as prospective therapeutic targets. This profibrotic stem cell variant in IPF was distinct from recently identified profibrotic stem cell variants in chronic obstructive pulmonary disease and may extend the notion that inappropriate accrual of minor and preexisting stem cell variants contributes to chronic lung conditions.


Assuntos
Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Miofibroblastos/patologia , Fibroblastos/patologia , Células-Tronco/metabolismo , Clonagem Molecular
14.
Ann Intern Med ; 176(2): 224-238, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36592456

RESUMO

DESCRIPTION: This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. METHODS: The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. AUDIENCE AND PATIENT POPULATION: The audience for this guideline includes all clinicians. The patient population includes adults with primary osteoporosis or low bone mass. RECOMMENDATION 1A: ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). RECOMMENDATION 1B: ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). RECOMMENDATION 2A: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; moderate-certainty evidence). RECOMMENDATION 2B: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests that clinicians use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation). RECOMMENDATION 4: ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in females over the age of 65 with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence).


Assuntos
Conservadores da Densidade Óssea , Fraturas Ósseas , Osteoporose , Médicos , Adulto , Feminino , Humanos , Masculino , Conservadores da Densidade Óssea/efeitos adversos , Denosumab/uso terapêutico , Difosfonatos/efeitos adversos , Fraturas Ósseas/prevenção & controle , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Ligante RANK/uso terapêutico
15.
FEBS Open Bio ; 13(3): 519-531, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36683396

RESUMO

Visceral leishmaniasis (VL) is among the most neglected tropical diseases in the world. Drug cell permeability is essential for killing the intracellular residing parasites responsible for VL, making cell-permeating peptides a logical choice to address VL. Unfortunately, the limited biological stability of peptides restricts their usage. Sequence-specific oligo-N-substituted glycines ('peptoids') are a class of peptide mimics that offers an excellent alternative to peptides in terms of ease of synthesis and good biostability. We tested peptoids against the parasite Leishmania donovani in both forms, that is, intracellular amastigotes and promastigotes. N-alkyl hydrophobic chain addition (lipidation) and bromination of oligopeptoids yielded compounds with good antileishmanial activity against both forms, showing the promise of these antiparasitic peptoids as potential drug candidates to treat VL.


Assuntos
Leishmania donovani , Leishmaniose Visceral , Peptoides , Humanos , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Peptoides/farmacologia , Peptoides/uso terapêutico , Biomimética , Peptídeos
17.
J Hand Surg Am ; 48(9): 954.e1-954.e10, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35610117

RESUMO

PURPOSE: Nerve transfer is the gold standard to restore shoulder abduction in acute brachial plexus injuries. The aim of this study was to compare the phrenic nerve (Ph) to the spinal accessory nerve (XI) as the donor nerve for this purpose. METHODS: A retrospective chart review was performed on 136 patients with acute brachial plexus injuries who received a nerve transfer of the shoulder with either the Ph (94 patients) or XI (42 patients). Each group was divided into 3 subgroups based on the recipient nerve. The maximum degree of shoulder abduction was recorded after 2 years of postoperative follow-up. A generalized estimating equation model was performed to examine the variables affecting shoulder abduction over time. RESULTS: The maximum degrees of shoulder abduction achieved were 61.9° ± 38.7° in patients with Ph and 51.1° ± 37.3° in patients with XI. More than M3 shoulder abduction was achieved by 67% of patients with Ph versus 59% of patients with XI. The regression analysis showed that the age at the time of surgery correlated more with the functional outcome over time than the choice of donor nerve. CONCLUSIONS: In multiple root brachial plexus injuries, the Ph exhibited similar outcomes to the XI for shoulder abduction. Our routine exploration of the supraclavicular plexus exposes the Ph conveniently for nerve transfer. The phrenic nerve should be considered as an alternative when the XI is not available or is reserved for secondary reconstruction. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Assuntos
Neuropatias do Plexo Braquial , Plexo Braquial , Transferência de Nervo , Adulto , Humanos , Ombro/cirurgia , Nervo Frênico/cirurgia , Neuropatias do Plexo Braquial/cirurgia , Estudos Retrospectivos , Plexo Braquial/lesões , Nervo Acessório/cirurgia , Amplitude de Movimento Articular/fisiologia
18.
J Reconstr Microsurg ; 39(4): 279-287, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36191593

RESUMO

BACKGROUND: The restoration of finger movement in total brachial plexus injuries (BPIs) is an ultimate challenge. Pedicled vascularized ulnar nerve graft (VUNG) connecting a proximal root to distal target nerves has shown unpredictable outcomes. We modified this technique by harvesting VUNG as a free flap to reinnervate median nerve (MN). We analyzed the long-term outcomes of these methods. METHODS: From years 1998 to 2015, 118 acute total brachial plexus patients received free VUNG to innervate the MN. Patients were followed up at least 5 years after the initial surgery. Donor nerves included the ipsilateral C5 root (25 patients) or contralateral C7 root (CC7 = 93 patients). Recovery of finger and elbow flexion was evaluated with the modified Medical Research Council system. Michigan Hand Score and Quick-DASH were used to represent the patient-reported outcomes. RESULTS: For finger flexion, ipsilateral C5 transfer to MN alone yielded similar outcomes to MN + MCN (musculocutaneous nerve), while CC7 had significantly better finger flexion when coapted to MN alone than to MN + MCN. Approximately 75% patients were able to achieve finger flexion with nerve transfer alone. For elbow flexion, best outcome was seen in the ipsilateral C5 to MCN and MN. CONCLUSION: In acute total BPI, the priority is to identify the ipsilateral C5 root to innervate MN, with concomitant innervation of MCN to establish the best outcomes for finger and elbow flexion. CC7 is more reliable when used to innervate one target (MN). LEVEL OF EVIDENCE: III.


Assuntos
Neuropatias do Plexo Braquial , Plexo Braquial , Articulação do Cotovelo , Transferência de Nervo , Humanos , Nervo Ulnar/transplante , Nervo Mediano/cirurgia , Neuropatias do Plexo Braquial/cirurgia , Plexo Braquial/cirurgia , Plexo Braquial/lesões , Transferência de Nervo/métodos , Resultado do Tratamento
19.
JAMA ; 328(12): 1250-1252, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36166040

RESUMO

This systematic review to support the 2022 US Preventive Services Task Force Recommendation Statement on screening for syphilis infection summarizes published evidence on the benefits and harms of screening for syphilis infection in asymptomatic, nonpregnant adults and adolescents at increased risk for syphilis infection.


Assuntos
Programas de Rastreamento , Sífilis , Adolescente , Adulto , Comitês Consultivos , Humanos , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/métodos , Serviços Preventivos de Saúde , Medição de Risco , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Estados Unidos
20.
J Health Econ Outcomes Res ; 9(2): 86-94, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36168593

RESUMO

Background: Epidural analgesia can be associated with high costs and postsurgical risks such as hypotension, despite its widespread use and value in providing opioid-sparing pain management. We tested the hypothesis that liposomal bupivacaine (LB) might be a reliable alternative to epidural analgesia in this real-world study. Objectives: To compare economic outcomes and hypotension incidence associated with use of LB and epidural analgesia for abdominal surgery. Methods: This retrospective analysis identified records of adults who underwent abdominal surgeries between January 2016 and September 2019 with either LB administration or traditional epidural analgesia using the Premier Healthcare Database. Economic outcomes included length of stay, hospital costs, rates of discharge to home, and 30-day hospital readmissions. Secondary outcomes included incidence of postsurgical hypotension and vasopressor use. Subgroup analyses were stratified by surgical procedure (colorectal, abdominal) and approach (endoscopic, open). A generalized linear model adjusted for patient and hospital characteristics was used for all comparisons. Results: A total of 5799 surgical records (LB, n=4820; epidural analgesia, n=979) were included. Compared with cases where LB was administered, cases of epidural analgesia use were associated with a 1.6-day increase in length of stay (adjusted rate ratio [95% confidence interval (CI), 1.2 [1.2-1.3]]; P<.0001) and $6304 greater hospital costs (adjusted rate ratio [95% CI], 1.2 [1.2-1.3]]; P<.0001). Cost differences were largely driven by room-and-board fees. Epidural analgesia was associated with reduced rates of discharge to home (P<.0001) and increased 30-day readmission rates (P=.0073) compared with LB. Epidural analgesia was also associated with increased rates of postsurgical hypotension (30% vs 11%; adjusted odds ratio [95% CI], 2.8 [2.3-3.4]; P<.0001) and vasopressor use (22% vs 7%; adjusted odds ratio [95% CI], 3.1 [2.5-4.0]; P<.0001) compared with LB. Subgroup analyses by surgical procedure and approach were generally consistent with overall comparisons. Discussion: Our results are consistent with previous studies that demonstrated epidural analgesia can be associated with higher utilization of healthcare resources and complications compared with LB. Conclusions: Compared with epidural analgesia, LB was associated with economic benefits and reduced incidence of postsurgical hypotension and vasopressor use.

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